Absorption, Distribution and Excretion
Systemic absorption and mode of action of dienestrol are undetermined.Estrogens diffuse into their target cells and interact with a protein receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).
ESTROGENS USED IN THERAPY ARE ... READILY ABSORBED THROUGH SKIN, MUCOUS MEMBRANES, AND GI TRACT. WHEN THEY ARE APPLIED FOR LOCAL ACTION, ABSORPTION IS OFTEN SUFFICIENT TO CAUSE SYSTEMIC EFFECTS. /ESTROGENS/
IN FACTORY WORKERS GYNECOMASTIA HAS FOLLOWED HANDLING OF DIETHYLSTIBESTROL WITHOUT GLOVES. /DIETHYLSTILBESTEROL/
URINARY EXCRETION RATE OF ESTROGENS IS QUITE SIMILAR WHETHER AGENTS ARE GIVEN ORALLY OR INTRAVENOUSLY, WHICH SUGGESTS THAT ABSORPTION OF MOST ESTROGENS FROM GI TRACT IS PROMPT & QUITE COMPLETE. /ESTROGENS/
ESTROGENS ARE PRACTICALLY INSOLUBLE IN WATER. WHEN DISSOLVED IN OIL AND INJECTED, THEY ARE RAPIDLY ABSORBED & QUICKLY METABOLIZED. ... INACTIVATION OF ESTROGEN IS CARRIED OUT MAINLY IN THE LIVER. /ESTROGENS/
For more Absorption, Distribution and Excretion (Complete) data for DIENESTROL (10 total), please visit the HSDB record page.

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Metabolism / Metabolites
Hepatic.
DIENESTROL YIELDS DIENESTROL-BETA-D-GLUCURONIDE IN RABBITS.
DIENESTROL IS A KNOWN METABOLITE OF DIETHYLSTILBESTROL IN PRIMATES & MICE; IT IS CONVERTED TO OMEGA-HYDROXY-DIENESTROL, WHICH IS EXCRETED IN CONJUGATED FORM ... RABBITS GIVEN ORAL DOSES OF DIENESTROL EXCRETED DIENESTROL GLUCURONIDE IN THEIR URINE ... .
RABBITS GIVEN ORAL DOSES OF DIENESTROL EXCRETED DIENESTROL GLUCURONIDE IN THEIR URINE ... .

Protein Binding
50 to 80%

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Interactions
Concurrent use with estrogens may alter the metabolism and protein binding of glucocorticoids, leading to decreased clearance, increased elimination half-life, and increased therapeutic and toxic effects of the glucocorticoids.
Estrogens may cause amenorrhea, interfering with effects of bromocriptine. /Estrogen/
Calcium supplements: concurrent use with estrogens may increase calcium absorption. /Estrogen/
Concurrent use with estrogens may potentiate the anti-inflammatory effects of endogenous cortisol induced by corticotropin. /Estrogen/
For more Interactions (Complete) data for DIENESTROL (9 total), please visit the HSDB record page.

[1]. J Chromatogr B Analyt Technol Biomed Life Sci . 2014 Apr 15:957:7-13.

Dienestrol is an olefinic compound that is hexa-2,4-diene substituted by 4-hydroxyphenyl groups at positions 3 and 4 respectively. It has a role as a xenoestrogen. It is a member of phenols and an olefinic compound.
Dienestrol is a synthetic, non-steroidal estrogen. It is an estrogen receptor agonist. Estrogens work partly by increasing a normal clear discharge from the vagina and making the vulva and urethra healthy. Using or applying an estrogen relieves or lessens: dryness and soreness in the vagina, itching, redness, or soreness of the vulva. Conditions that are treated with vaginal estrogens include a genital skin condition (vulvar atrophy), inflammation of the vagina (atrophic vaginitis), and inflammation of the urethra (atrophic urethritis).
Dienestrol has been reported in Magnolia obovata with data available.
A synthetic, non-steroidal estrogen structurally related to stilbestrol. It is used, usually as the cream, in the treatment of menopausal and postmenopausal symptoms.

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Drug Indication
For use in the treatment of atrophic vaginitis and kraurosis vulvae.

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Mechanism of Action
Dienestrol is a synthetic, non-steroidal estrogen. Estrogens passively diffuse into target cells of responsive tissues, complex with the estrogen receptors, and enter the cell's nucleus to initiate or enhance gene transcription of protein synthesis after binding to DNA.
ESTROGENS ARE FIRST BOUND WITH VERY HIGH AFFINITY TO A CYTOPLASMIC 8 S RECEPTOR PROTEIN, WHICH THEN DISSOCIATES INTO A 4 S WITH ESTROGEN ATTACHED. ... THE ESTROGEN COMPLEX IS CONVERTED TO A 5 S SPECIES THAT IS TRANSPORTED TO THE NUCLEUS, WHERE ULTIMATE BINDING OF ESTROGEN-CONTAINING COMPLEX OCCURS. /ESTROGENS/
THE ACTIVITY OF ... SYNTHETIC ... ESTROGENS DEPENDS ON PRESENCE OF HYDROXYL GROUPS @ EXTREMITIES OF THEIR MOLECULES ... HYDROXYLS ... INVOLVED IN BINDING WITH SPECIFIC RECEPTOR PROTEINS, PRESENT IN CYTOSOL OF CELLS IN TARGET ORGANS. /ESTROGENS/
At the cellular level, estrogens increase the cellular synthesis of DNA, RNA, and various proteins in responsive tissues. Estrogens reduce the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, leading to a reduction in release of follicle-stimulating hormone and luteinizing hormone from the pituitary. /Estrogen/

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Therapeutic Uses
Estrogens, Non-Steroidal
DIENESTROL, LIKE STILBESTROL, IS A NON-STEROIDAL ESTROGEN DERIVED FROM STILBENE. IT MAY BE ADMIN ORALLY OR APPLIED TOPICALLY. ITS USE ORALLY HAS NO ADVANTAGES OVER OTHER ORAL ESTROGENS, & NO ORAL PREPN ARE MARKETED. DIENESTROL IS PRIMARILY USED AS AN INTRAVAGINAL CREAM FOR ATROPHIC VAGINITIS OR PREPUBERTAL VULVOVAGINITIS.
MEDICATION (VET): SYNTHETIC ESTROGEN. THE DIACETATE FORM IS USED IN FEEDING TRIALS. PARENTERALLY, IN FUNCTIONAL STERILITY WHERE ADEQUATE ESTROGENS ARE LACKING FOR STIMULATION & MATURATION OF OVARIAN FOLLICLE IN CATTLE & OCCASIONALLY IN HORSES. ORALLY, FOR CHICKENS & TURKEYS TO IMPROVE TENDERNESS & APPEARANCE BY PROPER FAT DISTRIBUTION.
MEDICATION (VET): INCREASES FATTY LIVERS & SERUM CALCIUM, WHILE DECR BONE FRAGILITY IN CHICKENS. CAN BE USED INTRAVAGINALLY & INTRAUTERINE TO HELP RESTORE NORMAL EPITHELIAL GROWTH.
For more Therapeutic Uses (Complete) data for DIENESTROL (10 total), please visit the HSDB record page.

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Drug Warnings
DIENESTROL IS CONTRAINDICATED DURING PREGNANCY.
... DISADVANTAGE OF SOME SYNTHETIC ESTROGENIC CMPD IS THAT NAUSEA FOLLOWS USE OF ... MINIMUM EFFECTIVE DOSE IN SOME WOMEN, BUT ... NOT OVER 20% OF THOSE WHO USE MATERIALS CAREFULLY. IN SUCH WOMEN SYNTHETIC MATERIALS MUST BE REPLACED BY NATURAL PRODUCTS. /SYNTHETIC ESTROGEN/
Dienestrol has not been shown to be effective for any purpose during pregnancy, and use of the drug in pregnant women may cause severe harm to the fetus.
Dienestrol shares the toxic potentials of other estrogens, and the usual cautions, precautions, and contraindications associated with estrogen therapy should be observed.
For more Drug Warnings (Complete) data for DIENESTROL (18 total), please visit the HSDB record page.

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Pharmacodynamics
Estrogens diffuse into their target cells and interact with a protein receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).

C18H18O2

266.3343

266.131

C, 81.17; H, 6.81; O, 12.01

84-17-3

Dienestrol-d2;1346606-45-8

667476

White to off-white crystalline powder

1.129 g/cm3

395.4ºC at 760 mmHg

229ºC

181.4ºC

1.4800 (estimate)

4.604

2

2

3

20

318

0

OC1C=CC(C(C(C2C=CC(O)=CC=2)=CC)=CC)=CC=1

NFDFQCUYFHCNBW-SCGPFSFSSA-N

InChI=1S/C18H18O2/c1-3-17(13-5-9-15(19)10-6-13)18(4-2)14-7-11-16(20)12-8-14/h3-12,19-20H,1-2H3/b17-3+,18-4+

4-[(2E,4E)-4-(4-hydroxyphenyl)hexa-2,4-dien-3-yl]phenol

Dehydrostilbestrol; Restrol; Sexadien; Dienoestrol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~155 mg/mL (~582 mM)

Solubility in Formulation 1: 2.08 mg/mL (7.81 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (7.81 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (7.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)